Catecholamines are stored in stable, concentrated form inside storage granules in the nerve endings and in the adrenal gland. Our knowledge of how catecholamines are taken up into the storage granule is limited to the concept that there is some type of energy driven uptake process involving a carrier which acts to shuttle the catecholamines into the interior of the granule. According to one school of thought, a Mg ATPase located in the membrane acts as a proton pump and the resulting electrochemical gradients act as a driving force for the shuttle mechanism. Our knowledge of the carrier itself, its affinity for catecholamines and how the shuttle uses the energy provided by the electrochemical gradient is very limited. The long range goal of the principal investigator is to determine the mechanism by which catecholamines are transported into the storage granules. We will approach this problem by studying the carrier mechanism itself. Our studies will be directed towards identifying the carrier using (3H) (-) norepinephrine and (3H) reserpine as the binding ligands. We will determine the characteristics of this binding site and conditions required for binding of biogenic amines to this site. Some insight into the nature and molecular weight of the carrier will be determined. In addition, we have proposed a new model to explain how this shuttle system functions, and some studies will be directed towards providing this model.